PROJECT SUMMARY/ABSTRACT Head injury research has been highly visible in the mainstream news thanks to studies highlighting the significant deficits suffered by athletes exposed to repeated and severe head trauma, as well as due to injuries from proximity to IED's in international conflicts. Traumatic brain injury (TBI) is widely known to cause alterations in cognition and damage to structural white matter in the brain, which can lead to brain network dysfunction. It is also an associated risk factor for diagnosis of Alzheimer's disease (AD) and has been linked with an acute increase in levels of pathological proteins associated with AD (i.e., amyloid and tau). Head injury below the threshold for TBI, encompassing concussive and subconcussive impact, is an unfortunately even more common experience in everyday life. There is growing evidence that even mild head injuries such as these may negatively impact brain structure and function; however, the impact these concussive and subconcussive blows on cognition, brain networks, and pathology related to AD is still unclear. Even less is known about the long-term role of previous and repeated head injury and how it affects cognitive function over time. The purpose of this proposed study is to develop and implement a new instrument designed to obtain a detailed history of mild head injury and to investigate the impact of previous head injury on cognition, brain network organization, and neuropathological biomarkers of AD (i.e., amyloid and tau proteins) in cognitively normal older adults (ages 20-89). This fellowship will be utilizing participants from the Dallas Lifespan Brain Study (DLBS), a longitudinal study of cognitively normal individuals who are well-characterized with extensive neuropsychological testing and neuroimaging across multiple time points. Recent imaging breakthroughs have allowed us to measure cerebral tau proteins in living humans for the first time, and the DLBS is one of the few sites with access to this new radiotracer. The first aim of the study concerns the design and implementation of head injury self- report questionnaires in order to create indices of prior had injury frequency & severity. The second aim examines the relationship between these frequency and severity indices of head injury and major domains of cognition: episodic memory, executive functioning, processing speed, and language. In the third aim, these indices will be related to cerebral burden of amyloid and tau proteins using positron emission tomography imaging, and assess the potential interactive effect of having a genetic predisposition to AD. The last aim of this study will use structural and functional magnetic resonance imaging to compare these indices to cerebral white matter lesions and functional brain network connectivity.